Genetic Variant CPEB1:p.Phe3Ser (chr15-82647863-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001365243.1(CPEB1):c.8T>C(p.Phe3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,269,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

CPEB1
NM_001365243.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.412

Variant links:

Genes affected

CPEB1 (HGNC:21744): (cytoplasmic polyadenylation element binding protein 1) This gene encodes a member of the cytoplasmic polyadenylation element binding protein family. This highly conserved protein binds to a specific RNA sequence, called the cytoplasmic polyadenylation element, found in the 3' untranslated region of some mRNAs. The encoded protein functions in both the cytoplasm and the nucleus. It is involved in the regulation of mRNA translation, as well as processing of the 3' untranslated region, and may play a role in cell proliferation and tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CPEB1 links:

CPEB1-AS1 (HGNC:27523): (CPEB1 antisense RNA 1)

CPEB1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058113396).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CPEB1	NM_001365243.1 link	c.8T>C	p.Phe3Ser	missense_variant	Exon 1 of 12	NP_001352172.1
CPEB1	NM_030594.5 link	c.8T>C	p.Phe3Ser	missense_variant	Exon 1 of 12	NP_085097.3	Q9BZB8-3
CPEB1	NM_001387070.1 link	c.-276T>C		5_prime_UTR_variant	Exon 1 of 13	NP_001373999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CPEB1	ENST00000615198.4 link	c.8T>C	p.Phe3Ser	missense_variant	Exon 1 of 12	1	ENSP00000477715.1	Q9BZB8-3
CPEB1-AS1	ENST00000560650.1 link	n.94A>G		non_coding_transcript_exon_variant	Exon 1 of 4	1
CPEB1	ENST00000563519.1 link	n.159+357T>C		intron_variant	Intron 1 of 4	4
CPEB1	ENST00000566716.1 link	n.423+576T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000251

AC:

280

AN:

1117760

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

127

AN XY:

536164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.0000897

GnomAD4 genome

AF:

0.000112

AC:

AN:

151716

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8T>C (p.F3S) alteration is located in exon 1 (coding exon 1) of the CPEB1 gene. This alteration results from a T to C substitution at nucleotide position 8, causing the phenylalanine (F) at amino acid position 3 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.26

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.69

Sift4G

Pathogenic

0.0

Polyphen

0.020

Vest4

0.11

MVP

0.15

ClinPred

0.55

GERP RS

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.087

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over